Changing global markets have generated a dramatic shift in tobacco consumption from high-income countries (HICs) to low- and middle-income countries (LMICs); by 2030, more than 80% of the disease burden from tobacco use will fall on LMICs. Propelling this shift, opponents of tobacco control have successfully asserted that tobacco is essential to the economic livelihoods of smallholder tobacco farmers and the economy of tobacco-growing countries. This nexus of economic, agricultural and public health policymaking is one of the greatest challenges facing tobacco control efforts, especially in LMICs. To date, there is a lack of comparative, individual level evidence about the actual livelihoods of tobacco-growing farmers and the political economic context driving tobacco production. This comparative evidence is critically important to identify similarities and differences across contexts and to provide local evidence to inform policies and institutional engagement. Our proposed four-year project will examine the economic situation of smallholder farmers in two major tobacco-growing LMICs—Mozambique and Zimbabwe—and the political economy shaping farmers’ livelihoods and tobacco control efforts. We will collect and analyze the existing data and policy literature on the political economy of tobacco in these two countries. We will also implement household-level economic surveys of nationally representative samples of farmers. The surveys will be complimented with focus group discussions with farmers across the major tobacco-growing regions. Finally, we will interview key informants in these countries in order to illuminate the policy context in which tobacco production is perpetuated. The team will develop country-level reports and policy briefs that will inform two sets of dissemination workshops in each country with relevant stakeholders. We will also conduct workshops to present our findings to the survey and focus group participants, and other members of these tobacco-growing communities, so they can directly benefit from the research to which they are contributing.